反応 #2286393

ord-e4f4b799d6af4d91adebaae81f2027f1

反応方程式

CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1cnc(Br)s1
di(tert-butyl) 2-bromo-1,3-thiazol-5-ylimidodicarbonate
OB(O)c1ncccc1F
fluoropyridine boronic acid
CCO
ethanol
O=C([O-])[O-].[K+].[K+]
K2CO3
CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1cnc(-c2cncc(F)c2)s1
desired product
収率 73.0%
CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1cnc(-c2cncc(F)c2)s1
di(tert-butyl) 2-(5-fluoropyridin-3-yl)-1,3-thiazol-5-ylimidodicarbonate
収率 73.0%

溶媒

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    その他The flask was fitted with a reflux condenser
  2. 2
    温度was heated to reflux
  3. 3
    温度the reaction was cooled in an ice bath
  4. 4
    その他partitioned between aqueous saturated NaHCO3 and ethyl acetate
  5. 5
    その他The layers were separated
  6. 6
    抽出the aqueous layer was extracted once with ethyl acetate
  7. 7
    洗浄The combined organics were washed once with brine
  8. 8
    乾燥dried over MgSO4
  9. 9
    ろ過filtered
  10. 10
    濃縮concentrated
  11. 11
    その他This solid was triturated with 20% ethyl acetate/hexanes
  12. 12
    ろ過The solids were filtered off
  13. 13
    その他the filtrate evaporated
  14. 14
    その他to provide a residue which
  15. 15
    その他was purified via silica gel column chromatography (0 to 100% ethyl acetate/hexanes)

実験手順

To a 3-neck round bottom flask was added fluoropyridine boronic acid (4.55 g, 32.3 mmol), ethanol (54 mL), and aqueous K2CO3 solution (27 mL, 2.0 M, 53.8 mmol), followed by 50 mL toluene. To this mixture was added di(tert-butyl) 2-bromo-1,3-thiazol-5-ylimidodicarbonate (10.2 g, 26.9 mmol). Next, tetrakis(triphenylphosphine)palladium(0) (6.2 g, 5.4 mmol) was added in one portion. The flask was fitted with a reflux condenser and was heated to reflux. After 45 minutes, the reaction was cooled in an ice bath and partitioned between aqueous saturated NaHCO3 and ethyl acetate. The layers were separated and the aqueous layer was extracted once with ethyl acetate. The combined organics were washed once with brine, dried over MgSO4, filtered, and then concentrated. This solid was triturated with 20% ethyl acetate/hexanes. The solids were filtered off and the filtrate evaporated to provide a residue which was purified via silica gel column chromatography (0 to 100% ethyl acetate/hexanes) to afford the desired product as an off-white solid (7.74 g, 73% yield): mp 94-96° C.; 1H NMR (300 MHz, CDCl3) δ 8.91 (app t, J=1.3 Hz, 1H), 8.52 (d, J=3.0 Hz, 1H), 7.96 (ddd, J=9.2, 3.0, 1.8 Hz, 1H), 7.66 (s, 1H), 1.48 (s, 18H); ESIMS m/z 396 (M+1).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US09357780B2uspto-grants-2016_06